Regorafenib Treatment for Recurrent Glioblastoma Beyond Bevacizumab-Based Therapy: A Large, Multicenter, Real-Life Study

Background/Objectives: In the REGOMA trial, regorafenib demonstrated an overall survival advantage over lomustine, and it has become a recommended treatment for recurrent glioblastoma in guidelines. This study aimed to evaluate the effectiveness and safety of regorafenib as a third-line treatment for patients with recurrent glioblastoma who progressed while taking bevacizumab-based therapy. Methods: This retrospective, multicenter study in Turkey included 65 patients treated between 2021 and 2023 across 19 oncology centers. The main inclusion criteria were histologically confirmed isocitrate dehydrogenase (IDH)-wildtype glioblastoma, progression after second-line bevacizumab-based treatment, and an Eastern Cooperative Oncology Group (ECOG) performance status score of <= 2. Patients received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle. Results: The median age of the patients was 53 years (18-67 years), with a median progression-free survival of 2.5 months (95% Confidence Interval: 2.23-2.75) and a median overall survival of 4.1 months (95% CI: 3.52-4.68). The median overall survival was improved in patients who received subsequent therapy after regorafenib treatment compared with those who did not (p = 0.022). Progression-free survival was longer in patients with ECOG 0-1 than in those with ECOG 2 (p = 0.042). The safety profile was consistent with that of the REGOMA trial, with no drug-related deaths observed. Conclusions: Regorafenib shows good efficacy and safety as a third-line treatment for recurrent glioblastoma after bevacizumab-based therapy. This study supports the use of regorafenib and emphasizes the need for further randomized studies to validate its role and optimize treatment strategies.